Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane

Endpoint summary

Description of key information

The acute dermal toxicity of the substance was determined by experiment to exceed 2000 mg/kg bw. There are no relevant acute oral toxicity studies available for the test substance. Four oral acute toxicity studies were conducted with closely related structural analogues; the oral LD50 value was determined to be > 2000 mg/kg body weight in three of these studies and > 5000 mg/kg bw in one of these studies.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Limited documentation but relevant data given.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Adopted 24 February 1987

Deviations:

yes

Remarks:

limited documentation, limited information on test substance given, no necropsy performed

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: mean: 185 g (males), 150 g (females)
- Fasting period before study: 18 h before until 3 h after dosing

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2 % solution in water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 %
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg / kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation after 1, 6, 24 and 48 h, weighing after 24 h, 1 and 2 weeks
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Body weight:

No effect on body weight was noted.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 Nov - 02 Dec 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study. For read-across, maximum reliability score is 2.

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

limited information on test substance

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 255 ± 8.8 g, females: 172 ± 12.0 g
- Fasting period before study: overnight before substance application until 3 h after dosing
- Housing: animals were housed individually in polycarbonate cages
- Diet: RMH-B, Hope Farms, Woerden, The Netherlands, ad libitum
- Water: tap-water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 55 - 70
- Air changes: air conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5.5 mL/kg bw

Doses:

Pilot study: 1800, 3200 and 5000 mg/kg bw
Main study: 5000 mg/kg bw

No. of animals per sex per dose:

Pilot study: 1
Main study: 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed daily for clinical signs of toxicity, and individual body weights were determined weekly
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period, neither in the pilot nor in the main study.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Body weight:

No effect on body weight was noted.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Apr - 12 Jun 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (limited information on test material).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted in 1987

Deviations:

yes

Remarks:

limited data on test material

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD (SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: male rats: Charles River Laboratories, Inc., Hollister, CA, USA; female rats: Charles River Laboratories, Inc., Portage, MI, USA
- Age at study initiation: 6 - 13 weeks
- Weight at study initiation: 274 - 292 g (males) and 221 - 256 g (females)
- Fasting period before study: food, but not water, was withheld 17 to 20 h prior to administration
- Housing: 5 animals of the same sex were housed in suspended screen-bottom stainless steel cages
- Diet: Laboratory Rodent Diet #5001, PMI Feeds, Inc., ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 (days 0 through 3), 18 - 26 (days 4 through 14)
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 21 Apr 1997: To: 5 May 1997

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.11 mL/kg bw (average bulk density of 0.95 g/mL)

DOSAGE PREPARATION: calculation was done for each animal based on its fasted body weight

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were conducted at 1, 2.5, and 4 h after test material administration and daily thereafter for 14 days. Mortality checks were conducted twice a day (morning and afternoon) for 13 days after test material administration and again in the morning of Day 14. Body weights were determined before test material administration (Day 0), at Day 7 and at Day 14.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the study period.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period. According to the author one male animal exhibited soft stool 1 h post-dose and returned to normal appearance 2.5 h post-dose.

Body weight:

No effect on body weight was noted.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 Nov - 20 Nov 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study Limited details on test compound. For read-across, maximum reliability score is 2.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

: Limited details on test compound

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: ICO: OFA-SD (IOPS Caw)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Crédo, France
- Age at study initiation: 6 weeks
- Weight at study initiation: males: 173 ± 3 g, females: 144 ± 7 g
- Housing: 5 animals per polycarbonate cage (48x27x20 cm)
- Fasting period before study: 18 h before until 4 h after dosing
- Diet: ad libitum (Rats - Mice substance ref. A04 C)
- Water: ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.13 mL taking into account the specific gravity of 0.94

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily, weighing on Days 1, 5, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology

Statistics:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

Hypokinesia was observed 2 and 4 h after treatment. From Day 2 to the end of the study, no clinical signs were observed.

Body weight:

Normal body weight gain

Gross pathology:

No apparent abnormalities

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Four Klimisch 2 studies are available.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 June 2010 To 08 July 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 21.5ºC
- Humidity (%): 41 - 78%
Temporary deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificialfluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 24 June 2010 To 08 July 2010

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg (2.105 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Dose level (volume): 2000 mg/kg (2.105 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: none.

Statistics:

None.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Chromodacryorrhoea (snout) was noted for two males and two females on Day 1. One of these females also showed lethargy and ptosis on Day 1. No further clinical signs were observed.

Body weight:

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 2 study

Additional information

Four oral acute toxicity studies are available for read-across substances:

In the first study conducted with CAS 11138-60-6 in accordance with OECD Guideline 401, the oral LD50 value in ICO: OFA-SD (IOPS Caw) rats was found to be > 2000 mg/kg body weight.

In the second study conducted with CAS 78-16-0 in accordance with OECD Guideline 401, the oral LD50 value in Crl:CD (SD)BR rats was determined to be > 2000 mg/kg body weight.

In the third study conducted with CAS 91050-89-4 in accordance with OECD Guideline 401, the oral LD50 value in Crl:CD (SD)BR was determined to be > 2000 mg/kg body weight.

In the fourth study with CAS 78-16-0 in accordance with EU Method B.1, the oral LD50 value in Wistar rats was determined to be > 5000 mg/kg body weight.

In a study conducted in accordance with OECD Guideline 402, the dermal LD50 value of decanoic acid, mixed esters with heptanoic acid, octanoic acid and trimethylolpropane in Wistar rats was established to exceed 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint

No one study could be selected as 4 studies are available with read-across substances (all Klimisch 2 providing LD50 values of > 2000 mg/kg bw and >5000 mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint

In accordance with column 2 of Annex VIII, the acute inhalation test (as required in section 8.5.2.) does not need to be performed because the substance is of sufficiently low vapour pressure to preclude exposure via inhalation at significant volumes.  Dermal exposure is considered to be the appropriate route of exposure and has been assessed accordingly.

Justification for selection of acute toxicity – dermal endpoint

Only 1 study is available with the test substance.

Justification for classification or non-classification

Based on the above mentioned results, classification according to the CLP Regulation (EC)1272/2008 and the Dangerous Substance Directive 67/548/EC is not necessary.

A report justifying the read-across approach is included in IUCLID Chapter 13.